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Biomedical subjects

H J Markowitsch

Publications and source records attributed to H J Markowitsch.

At least 127 records · Page 7Linked to original sources
PubMed1982

Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man.

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.

Afferent Pathways↗
PubMed1982

Epidural kainate, but not ibotenate, produces lesions in local and distant regions of the brain. A comparison of the intracerebral actions of kainic acid and ibotenic acid.

Epidural placement of ibotenic acid (Ibo) is described as a new technique for easy and successful lesioning of cortical neurons. The method works reliably without apparent damage to passing or underlying fibers and without causing distant lesion effects. In rats, the favorable effects of epidural placement of Ibo on behavior and on neuronal tissue were compared with and found to contrast with those of kainic acid (KA). Survival periods of 2, 4, 6, and 8 days were allowed for animals of each group. The effects of Ibo from Amanita muscaria were compared to those from Amanita pantherina. Local cortical lesions after epidural placement of KA and Ibo were compared with those after subdural placement. The effects resulting from covering a small surface of the dura with Ibo were compared with those resulting from covering a large surface. Epidural placement of KA and Ibo resulted in neuronal damage of the underlying cortex, 0.4 mg of KA leading to approximately the same lesion extent as 0.5 mg of Ibo. Epidural and subdural lesion effects were found to be similar both for KA and Ibo. The most striking difference between epidural application of KA and Ibo was that KA lesions resulted in a considerable number of damaged areas remote from the local cortical lesion, whereas even 10-times higher doses of Ibo (measured in moles) did not produce any observable neuronal damage outside the local lesion. From these results it is suggested that Ibo has to be favored over KA when local neuronal lesions are desired. Furthermore, epidural placement of Ibo is proposed as an effective technique for producing circumscribed cortical lesions.

Animals↗
PubMed1982

Retention performance of a learned delayed-alternation task after chemical lesions of the cats mediodorsal nucleus.

The mediodorsal nucleus of the thalamus was lesioned in cats, which had learned a spatial delayed-alternation task. Lesions were carried out with kainic acid or ibotenic acid. From altogether 29 cats, 9 cats with bilateral and 6 cats with unilateral lesions of the mediodorsal nucleus together with a control group of 4 cats, were included in the final data analysis. Lesions in the operated cats destroyed variable portions of the mediodorsal nucleus. Consistently, however, neither the midline nuclei, situated next to the damaged mediodorsal nucleus, nor fiber tracts traversing or by-passing the mediodorsal nucleus, were damaged. Furthermore, remote lesion effects were not detected either in the diazepam-pretreated cats with kainic acid-induced lesions or in the ibotenic acid-lesioned animals. Cats injected with ibotenic acid at a concentration 8-fold higher than the kainic acid solution, showed smaller thalamic lesions than kainic acid-injected cats. A direct correlation was found between the extent of neuronal damage within the mediodorsal nucleus and the degree of the behavioral impairment. Cats with complete or almost complete bilateral lesions of the mediodorsal nucleus manifested severe deficits in retention of the delayed-alternation task, while cats with small, bilateral lesions of the mediodorsal nucleus or with unilateral lesions were impaired less severely or even not at all.

Animals↗
PubMed1982

Single and combined lesions of the cats thalamic mediodorsal nucleus and the mamillary bodies lead to severe deficits in the acquisition of an alternation task.

The acquisition of a spatial alternation task was tested in five groups of adult cats. Two groups were used for control; one of them consisted of nonlesioned cats, the other of cats with chemical lesions (ibotenic acid) of the ventral tegmental area. The other three groups of cats received chemical lesions of the mediodorsal nucleus of the thalamus, the mamillary bodies, or of both structures together. Cats with lesions of the ventral tegmental area were non-significantly impaired in comparison to non-lesioned cats in the acquisition of the task. Cats with lesions of the mediodorsal nucleus, the mamillary bodies, or with combined lesions of both structures were significantly impaired, compared to the two control groups; among each other, however, their performance rates were similar. As none of the cats with single or combined lesions of the mamillary and the mediodorsal nuclei manifested observable abnormalities with respect to motor, motivational, or emotional behavior during their testing period, it is concluded that their--compared to the other two groups--inferior performance was due to a memory defect. As all three kinds of lesions resulted in a similar defect, it is suggested that the mamillary and the mediodorsal nuclei transmit information to one or more common target area(s), which is (are) dependent on information from either nucleus to operate effectively.

Animals↗
PubMed1982

Widespread cortical projections of the hippocampal formation in the cat.

Efferent projections from the hippocampal formation to the cat's cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cortex of 31 cats were injected with small amounts of horseradish peroxidase. All subregions of the hippocampal formation were screened for labeled cells. It was found that, with the exception of the entorhinal injections, only subicular areas of the hippocampal formation contain labeled neurons. When HRP was injected into the entorhinal cortex, labeled cells are also found in the hippocampus proper. The most dense projection from the subicular cortex is directed to the medial part of the cortical hemisphere. Here, cingulate, retrosplenial and medial prefrontal fields receive a substantial number of subicular efferents. Furthermore, the entorhinal cortex is reached by a number of axons originating in the subicular area. Scarce projections from the subicular cortex terminate in the dorsal prefrontal, temporal, parietal and prepiriform cortex. It is suggested that the projection from the subicular cortex to the neocortical areas of the frontal pole (medial prefrontal cortex) is of special importance as it may constitute a link between the association areas of the neocortex and those regions of the limbic system thought to play a role in memory (subicular cortex, mamillary bodies, anterior thalamus, cingulate gyrus).

Animals↗
PubMed1982

Behavioral effects of systemic injection of ibotenic acid manifested without neuromorphological correlates.

Behavioral and neuromorphological effects of intraperitoneally injected ibotenic acid (IBO) were investigated in rats. These injections led to a number of marked behavioral disturbances which ultimately resulted in the death of 6 of the 13 IBO-treated rats. Despite marked changes in behavior, no morphological changes could be detected in the brain tissue of the surviving rats.

Animals↗
PubMed1982

Subtle but distinct impairments of rats with chemical lesions in the thalamic mediodorsal nucleus, tested in a radial arm maze.

The performance of rats trained in a radial arm maze was tested before and after chemical lesions of the thalamic mediodorsal nucleus or the ventral tegmental area. Their behavior was compared with that of a sham-operated control group. Lesions were produced with ibotenic acid, a compound that selectively destroys neurons while apparently leaving fibers of passage intact. Results revealed no intergroup difference in the number of errors performed when all six trials were given in one session without interruption. The group with mediodorsal lesions made, however, significantly more errors than either of the other two groups when a delay of 1 hr was interposed between the first four and the last two trials. Furthermore, these rats differed from rats of the other groups in the number of sessions necessary to reach criterion, in the time needed to finish a session, and in the directness with which a goal was approached. Rats with lesions of the ventral tegmental area did not differ from rats of the sham-operated control group in any of the measures taken. It is suggested that the deficits of rats with mediodorsal lesions resemble qualitatively those found in human patients with lesions of the mediodorsal nucleus.

Animals↗
PubMed1982

Organization of cortical afferents to the prefrontal cortex in the bush baby (Galago senegalensis).

Cortical afferents to the prefrontal cortex were studied in 10 bush babies (Galago senegalensis) by means of somatopetal transport of horseradish peroxidase. The lateral injections invariably labeled neurons in the temporal cortex and in most cases also in the insular and parietal regions. In some of these brains the cingulate and retrosplenial areas contained labeled perikarya. Injections into the medial cortex, on the other hand, consistently labeled cell bodies in the cingulate cortex, but not in the insular, temporal and parietal regions. When both lateral and medial sites of the bush baby's prefrontal cortex are considered together, apparently fewer cortical areas (as defined by Brodmann's cytoarchitectonic maps) project to the prefrontal cortex in the bush baby than in the rhesus monkey. This statement holds for both ipsi- and contralateral projections.

Afferent Pathways↗
PubMed1981

No detectable remote lesions following massive intrastriatal injections of ibotenic acid.

Behavioral and anatomical consequences of particularly large intrastriatal injections of ibotenic acid are described. Only in the rat with the largest injection, which encompassed almost the entire frontal lobe, were enduring aphagia and adipsia observed; epileptic attacks were, however, not detectable in this or in any other of the rats. In spite of the massiveness of the lesion, neither remote lesions nor damage to passing fibers was observed. It is therefore suggested to substitute kainic acid by ibotenic acid for the production of local, discrete brain lesions.

Animals↗
PubMed1981

Widespread cortical projections of the ventral tegmental area and of other brain stem structures in the cat.

Thirty-three cat brains with injections of horseradish peroxidase in various regions of the cerebral cortex were screened for afferent projections from the ventral tegmental area, the locus ceruleus, and the parabrachial nuclei. All three structures were found to project to rather divergent parts of the cortex, including regions in the posterior half of the hemisphere. These results, especially for the ventral tegmental area and, to a lesser degree, for the parabrachial neurons, disagree with most of the target loci of established cortical afferents in the rat. Though our results might be attributed to species differences in the cortical innervation of brain stem structures, we prefer explanations which emphasize different densities in the distribution of brain stem afferents to the cortex, and/or which suggest different cortical targets of catecholaminergic and noncatecholaminergic neurons.

Afferent Pathways↗
PubMed1981

Delayed-alternation performance after kainic acid lesions of the thalamic mediodorsal nucleus and the ventral tegmental area in the rat.

The relative importance of two subcortical structures, projecting to the rat's prefrontal cortex, in mediation of delayed-alternation performance, was tested. These structures, the thalamic mediodorsal nucleus and the ventral tegmental area, were lesioned with kainic acid after the rats had learned a spatial delayed-alternation task. It was found that both structures are apparently involved to a similar degree in the performance of this task and that the behavior of both experimental groups differed from that of a sham-operated control group of rats.

Afferent Pathways↗
PubMed1981

Cortico-prefrontal afferents in the guinea pig.

The prefrontal cortex of the guinea pig was investigated in a search for afferents from cortical areas outside the frontal lobe using the horseradish peroxidase retrograde tracing technique. Based on afferents from the medial, the lateral, and from both parts of the thalamic mediodorsal nucleus, three prefrontal subregions were defined, namely the sulcal (within and above the rhinal sulcus), the medial (anterior and superior to the genu of the corpus callosum), and the fronto-polar subfield. Only the fronto-polar region was found to receive afferents from insular, cingulate, retrosplenial, parietal, and temporal cortical fields. Both of the other subfields received afferents only from neighboring cortical regions: the medial subfield from cingulate and retrosplenial areas and the sulcal subfield from the insular cortex. For all three subregions, the number of labeled cells was found to be small. These results were interpreted with caution, as extent and subdivisions of the guinea pig's prefrontal cortex and its comparability with that of other species depend considerably on the criteria used.

Afferent Pathways↗
PubMed1981

Prefrontal cortex of the mouse defined as cortical projection area of the thalamic mediodorsal nucleus.

In the mouse small amounts of horseradish peroxidase were injected iontophoretically into different portions of the frontal lobe. Out of a large number of mice, 18 with typical injections which together covered most of the anterior half of the cortex were selected, and their retrogradely labeled thalamic cells were described and illustrated in detail. Special emphasis was laid on the cortical projections of the mediodorsal nucleus which were considered to define locus and extent of the prefrontal cortex. The results reveal that topographically the extent of the mouse, prefrontal cortex closely resembles that of the rat, another species of the rodent order. It includes a small area within and dorsal to the rhinal sulcus and a comparatively larger region within the medial half of the anterior cortex. Furthermore, the dorsal tip of the frontal pole is reached by a considerable number of afferents from the mediodorsal nucleus. Whether this last projection also exists in the rat is still disputed. As in the rat, only the sulcal prefrontal cortex seems to be reached by mediodorsal cells alone, whereas the rest of the prefrontal cortical fields have overlapping projections from the anteromedial nucleus. Though a considerable area within the frontal lobe of the mouse is reached by mediodorsal afferents, the significance and usefulness of this definition of the prefrontal cortex is questioned.

Animals↗
PubMed1981

Prefrontal cortex of the guinea pig (Cavia porcellus) defined as cortical projection area of the thalamic mediodorsal nucleus.

The cortical projection area of the thalamic mediodorsal nucleus (MD) was investigated using the horseradish peroxidase technique. Distinct relationships between subdivisions of MD and of the prefrontal cortex were established: the medial sector of MD projects to sulcal cortex dorsal to the rhinal fissure and to the lateral frontopolar region; the lateral sector of MD reaches mainly cortex within the medial part of the hemisphere from the frontopolar region up to a mid corpus callosal level. The projection area of the lateral sector of MD overlaps with the projection fields of the paratenial and anteromedial nuclei. It is concluded that the guinea pig's prefrontal cortex, defined as the projection area of MD, has strong similarities with the prefrontal cortices of rats and rabbits, that is with the prefrontal cortices of species of two different orders.

Animals↗
PubMed1981

Delayed-alternation performance after selective lesions of the medial and sulcal prefrontal cortex of the guinea pig.

The sulcal or medial subdivision of the prefrontal cortex of the guinea pig was ablated after the animals had learned a spatial delayed-alternation task. Retention of this task was significantly impaired only after ablation of the medial prefrontal cortex. As the most critical cortical region for delayed-alternation performance in the rat is also situated in the medial prefrontal cortex, our findings suggest a close functional correspondence of the prefrontal cortices of these rodent species.

Afferent Pathways↗
PubMed1980

Delayed-alternation performance after selective lesions within the prefrontal cortex of the cat.

On the basis of new neuroanatomical findings on relationships between subregions of the mediodorsal thalamic nucleus and the prefrontal cortex of the cat, it was attempted to investigate the relative importance of prefrontal subfields with the aim of obtaining evidence in favor of a functional inequality of different prefrontal subfields. Four areas, named presylvian (PRS), proreal (PR), dorsomedial (DM), and orbito-insular (OI) sectors, were ablated successfully in 30 adult animals. Performance of a 10-sec delayed-alternation task was compared pre- and postoperatively. Furthermore, most of the cats had to learn an extension of this task postoperatively, using a 20-sec delay period, and lastly, these animals were subjected to an extinction test. Significant performance differences were obtained between cats of different groups in all three tasks. Lesions of subregion PR, and even more of subregion PRS, led to severe behavioral deterioration, whereas lesions of subregion OI were without effect, when compared with the behavior of a sham-operated control group. PRS-cats, furthermore, showed motor disturbances during the first postoperative week. The results obtained suggest that it is possible to subdivide the cat's prefrontal cortex functionally. In addition, it is hypothesized that behavioral changes in cats of groups PRS and PR are due to an inability to use kinesthetic information properly.

Animals↗